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Cholesterol

Cholesterol. exogenous (dietary) cholesterol delivered to liver via chylomicron remnants. endogenous cholesterol synthesized primarily in the liver from AcCoA (extrahepatic tissues also synthesize cholesterol) in the liver, cholesterol is either converted to

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Cholesterol

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  1. Cholesterol • exogenous (dietary) cholesterol delivered to • liver via chylomicron remnants. • endogenous cholesterol synthesized primarily • in the liver from AcCoA (extrahepatic tissues • also synthesize cholesterol) • in the liver, cholesterol is either converted to • bile salts or to cholesterol esters and packaged • into VLDLs. • Peripheral tissues obtain most of their exogenous • cholesterol from LDLs and convert it back to • cholesterol for use in membranes or store in • cholesterol ester droplets. • LDLs deliver cholsterol to the tissues - HDLs • circulate it back to the liver. • Excess cholesterol is disposed of by the liver as • bile salts.

  2. Lipoproteins-1 • hydrophobic core (TAGS, cholesterol esters) • hydrophilic surface (P-lipids, cholesterol, and • apolipoproteins) • Function • transport of lipids in blood • Types of lipoproteins • (classified according to density) • chylomicron • very low density (VLDL) • intermediate density (IDL) • low density (LDL) • high density (HDL) • Protein content increase, lipid decreases as density • increases. % TAGS 8% 85% Chylomicron VLDL IDL LDL HDL % Protein 2% 33%

  3. Chylomicron: • VLDL: • 85% TAG, 4% chol., 8% protein • 80 -500nm • formed in intestinal epithelial cells • deliver exogenous TAGS to tissue • ApoCII activates lipases in capillary cell • walls releasing FFA to tissue • chylomicron remnants return to liver where • they bind to ApoE receptor and are taken up • 1/2 life in blood - 4-5 minutes • 50% TAGs, 22% choles., 10% protein • 30 -100 nm • formed in liver • deliver endogenous lipids to other tissues • (mainly muscle and fat cells) • ApoCII activates lipases in capillary cell • walls releasing FFA to tissue • converted to IDLs and LDL as lipids are • released Lipoproteins-2

  4. IDL: (31% TAGs, 29% choles., 18% protein) • LDL: “bad” cholesterol • formed from VLDLs as lipids removed • some IDLs return to liver • rest converted to LDLs by further removal • of lipids • 10% TAGs, 45% choles., 25% protein • 25 - 30 nm • formed as lipids removed from VLDLs • and IDLs. • all Apolipoproteins lost except ApoB100 • bind to LDL receptor via ApoB100 and • taken up by endocytosis by hepatic and other • tissues (50-75% taken up by liver). Primary • mode of cholesterol delivery to tissues. • Synthesis of LDL receptor is inhibited by • high levels of intracellular cholesterol and • stimulated by low levels of cholesterol. • Therefore, cholesterol uptake is closly • matched to intracellular cholesterol levels. Lipoproteins-3

  5. Lipoproteins-4 • HDL: “good” cholesterol • 8% TAGs, 30% choles., 33% protein • 7.5 - 10 nm • formed in liver • scanvenge cholesterol from cell surfaces • and other lipoproteins and deliver it to liver. • Convert cholesterol to cholesterol ester • bind to “scanvenger receptor” on liver cell • surface - cholesterol esters taken up and • HDLs released and reenter circulation.

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